Experimenting with Training a Neural Network in Transkribus to Recognise Text in a Multilingual and Multi-Authored Manuscript Collection

This work aims at developing an optimal strategy to automatically transcribe a large quantity of uncategorised, digitised archival documents when resources include handwritten text by multiple authors and in several languages. We present a comparative study to establish the efficiency of a single multilingual handwritten text recognition (HTR) model trained on multiple handwriting styles instead of using a separate model for every language. When successful, this approach allows us to automate the transcription of the archive, reducing manual annotation efforts and facilitating information retrieval. To train the model, we used the material from the personal archive of the Dutch glass artist Sybren Valkema (1916–1996), processing it with Transkribus

NEW PHARMACOLOGICAL TOOLS FOR AUTISM RESEARCH: OXYTOCIN RECEPTOR MUTANT MICE AND ZEBRAFISH AS NEUROBEHAVIOURAL MODELS

Autism is a neurodevelopmental disorder which is characterized by severe and pervasive impairment in reciprocal socialization, qualitative impairment in communication and repetitive or stereotyped behaviour associated to resistance to change. Oxytocin (OT) is a peptidic hormone best known for its role in lactation and parturition. Recently, it has been also shown by several studies involving different lines of knock-out mice to play an important role in the central nervous system (CNS) by acting on the regulation of social, emotional, aggressive behaviour and on learning and memory. Furthermore, prosocial effects following OT administration in humans have been shown. The link between OT and autism has already been traced in preliminary clinical studies as autism affected patients received a beneficial outcome from treatment with OT. Pharmacokinetic (very short half-life), pharmacodynamic (unspecific binding to vasopressin (AVP) receptors) properties and the presence of peripheral side effects of OT, though, make this peptide an unsuitable target for a future clinical use. It is important, in this perspective, to characterize specific animal models in order to validate the use of OT analogs with more suitable characteristics for preclinical research. To this end, a characterization of the behavioural phenotype of OTR knock-out mice (OTR-/-) and heterozygous littermates (OTR+/-) in comparison with their wild type counterparts (OTR+/+) has been carried out. General home cage behaviour, sensory, motor abilities and emotional behaviour were not affected by the altered genotype. Interestingly, both and OTR+/- and OTR-/- mice exhibited a significant social impairment as quantified in both the sociability and social novelty tests. Furthermore, OTR-/- mice displayed much higher levels of aggression when facing a stranger mouse as a higher number of attacks and tail rattlings has been registered in the neutral cage paradigm. Moreover, when tested in the reversal phase of a T-maze task for their cognitive flexibility, OTR-/- showed a profound impairment in responding to the changes applied in their established routine. All in all, the OTR mutant mouse model provides full range autism-related aberrant behaviours, displaying social impairments, altered aggressive behaviour, a strong resistance to change and stereotyped behaviour. Mechanisms underlying the aberrant phenotype revealed by mutant mice were investigated through autoradiographic binding experiments for both OTR and vasopressin 1A receptor (V1aR) distribution. In addition, pharmacological treatments with OT, AVP and V1aR antagonist SR49059 were done. Binding experiments were carried out in specific brain areas known to exert a key role in integrating the processing of olfactory information that is crucial to regulate social and emotional behaviour in rodents. OTR-/- animals displayed an almost undetectable OTR binding in all tested areas. Furthermore, a slight compensatory up-regulation of V1aR in the hippocampus and a significant down-regulation of the V1aR expression in the anterior olfactory nucleus, amygdala, ventral pallidum and lateral septum were found. As for heterozygous mutants their phenotype appeared as halfway between the wild type and knock out counterparts for OTR binding sites and V1aR binding has been subjected to a slight reduction in ventral pallidum and anterior olfactory nucleus only. Hence, the previously mentioned aberrant behavioural phenotype displayed by OTR mutant mice could be due to an altered OT/AVP receptors concentration in crucial brain areas. Interestingly, intracerebroventicular treatment with both OT and AVP (0.5ng/mouse) in mutant mice was able to rescue the impairment shown in all behavioural tasks. Furthermore, pre-treatment with V1aR antagonist SR49059 (0.5 ng/mouse), which per se did not exert any effect, in association with OT, blocked the social, aggressive and cognitive enhancing effects of the neuropeptide. Our results suggest a strong involvement of AVP, alongside OT, and in particular the subtype 1A of the AVP receptor, in the modulation of social abilities and cognitive flexibility of OTR mutant mice. Finally, as an increasing interest for the use of zebrafish for social behavioural analyses to study the genetic basis of behaviour is rising, we also evaluated zebrafish potential as a screening tool for neuropsychiatric diseases involving deficits in social behaviour. To this end, we analyzed the effect of OT, AVP but most importantly isotocin (ISO) and vasotocin (AVT) (zebrafish homologues of OT and AVP, respectively) using the shoaling preference test as social paradigm. Dose-response parabolic curves were obtained and all neuropeptides showed significant efficacy in enhancing social interaction, suggesting the involvement of the oxytocin/vasopressin systems and their analogs in the modulation of zebrafish social behaviour. In conclusion, our findings indicate that OTR-/- and in part OTR+/- mice display autistic-like symptoms rescued by administration of AVP and OT to young adult animals. The OTR mutant mouse is thus instrumental to investigate the neurochemical and synaptic abnormalities underlying autistic-like disturbances and to test new strategies of pharmacological intervention. We also suggest the use of zebrafish as an alternative animal model for the study of social behaviour, especially as a screening tool: future studies involving new molecules acting on OT and AVP systems will be carried out, taking advantage of this new promising model

Cancer incidence in pet dogs: findings of the Animal Tumor Registry of Genoa, Italy.

Background: The occurrence of spontaneous tumors in pet animals has been estimated in a few European and North American veterinary cancer registries with dissimilar methodologies and variable reference populations. Objectives: The Animal Tumor Registry (ATR) of Genoa, Italy, was established in 1985 with the aim of estimating the occurrence of spontaneous tumors in dogs. Methods: Six thousand seven hundred and forty-three tumor biopsy specimens were received from local veterinarians in the Municipality of Genoa between 1985 and 2002. Three thousand and three hundred and three (48.9%) biopsy specimen samples were diagnosed as cancer and were coded according to the International Statistical Classification of Diseases (ICD-9). Results: Mammary cancer was the most frequently diagnosed cancer in female dogs, accounting for 70% of all cancer cases. Incidence of all cancers was 99.3 per 100,000 dog-years (95% CI: 93.6–105.1) in male dogs and 272.1 (95% CI: 260.7–283.6) in female dogs. The highest incidence rates were detected for mammary cancer (IR = 191.8, 95% CI: 182.2–201.4) and for non-Hodgkin's lymphoma (IR = 22.9, 95% CI: 19.7–26.5) in bitches and for non-Hodgkin's lymphoma (IR = 19.9, 95% CI: 17.4–22.7) and skin cancer (IR = 19.1, 95% CI: 16.6–21.8) in male dogs. All cancer IR increased with age ranging between 23.7 (95% CI: 18.4–30.1) and 763.2 (95% CI: 700.4–830.1) in bitches and between 16.5 (95% CI: 12.8–21.1) and 237.6 (95% CI: 209.1–269.0) in male dogs aged ≤3 years and >9–11 years. Conclusion: This study summarizes the work done by the ATR of Genoa, Italy, between 1985 and 2002. All cancer incidence was 3 times higher in female than in male dogs, a difference explained by the high rate of mammary cancer observed in bitches. Because a biopsy specimen was required to make a cancer diagnosis, cancer rates for internal organs cancers, such as respiratory and digestive tract cancers may have been underestimated in the study population

Elastic scattering with weakly bound projectiles

Possible effects of the break-up channel on the elastic scattering threshold anomaly has been investigated. We used the weakly bound 6,7Li nuclei, which is known to undergo break-up, as projectiles in order to study the elastic scattering on a 27Al target. In this contribution we present preliminary results of these experiments, which were analyzed in terms of the Optical Model and compared with other elastic scattering data using weakly bound nuclei as projectile. © 2007 American Institute of Physics.Fil:Figueira, J.M. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.Fil:Fernández Niello, J.O. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.Fil:Arazi, A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.Fil:Capurro, O.A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.Fil:Martí, G.V. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.Fil:Pacheco, A.J. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina

9^9Be+120^{120}Sn scattering at near-barrier energies within a four body model

Cross sections for elastic and inelastic scattering of the weakly-bound $^9$Be nucleus on a $^{120}$Sn target have been measured at seven bombarding energies around and above the Coulomb barrier. The elastic angular distributions are analyzed with a four-body continuum-discretized coupled-channels (CDCC) calculation, which considers $^9$Be as a three-body projectile ($\alpha$ + $\alpha$ + n). An optical model analysis using the S\~ao Paulo potential is also shown for comparison. The CDCC analysis shows that the coupling to the continuum part of the spectrum is important for the agreement with experimental data even at energies around the Coulomb barrier, suggesting that breakup is an important process at low energies. At the highest incident energies, two inelastic peaks are observed at 1.19(5) and 2.41(5) MeV. Coupled-channels (CC) calculations using a rotational model confirm that the first inelastic peak corresponds to the excitation of the 2$_1^+$ state in $^{120}$Sn, while the second one likely corresponds to the excitation of the 3$_1^-$ state.Comment: 11 pages, 9 figures. Accepted as PR

Comprehensive study of reaction mechanisms for the Be9+Sm144 system at near- and sub-barrier energies

The delayed x-ray detection technique was used to measure complete and incomplete fusion cross sections for the $^{9}\mathrm{Be}+^{144}\mathrm{Sm}$ reaction at sub- and near-barrier energies. Elastic and inelastic scattering for this system were also measured. Reaction cross sections were derived and the transfer cross sections of one neutron were calculated. The suppression of complete fusion above the barrier, of the order of 10%, is attributed to $^{9}\mathrm{Be}$ breakup and is considerably smaller than the value of 30% found for the $^{9}\mathrm{Be}+^{208}\mathrm{Pb}$ system

Effect of the break-up on the fusion and elastic scattering of weakly bound projectiles on 64^{64}Zn

We study the behavior of the fusion, break-up, reaction and elastic scattering of different projectiles on $^{64}$Zn, at near and above barrier energies. We present fusion and elastic scattering data with the tightly bound $^{16}$O and the stable weakly bound $^{6}$Li, $^{7}$Li and $^{9}$Be projectiles. The data were analyzed by coupled channel calculations. The total fusion cross sections for these systems are not affected by the break-up process at energies above the barrier. The elastic (non-capture) break-up cross section is important at energies close and above the Coulomb barrier and increases the reaction cross sections. In addition we also show that the break-up process at near and sub-barrier energies is responsible for the vanishing of the usual threshold anomaly of the optical potential and give rise to a new type of anomaly.Comment: 24 pages, 10 figure

A quinolin-8-ol sub-millimolar inhibitor of UGGT, the ER glycoprotein folding quality control checkpoint

Misfolded glycoprotein recognition and endoplasmic reticulum (ER) retention are mediated by the ER glycoprotein folding quality control (ERQC) checkpoint enzyme, UDP-glucose glycoprotein glucosyltransferase (UGGT). UGGT modulation is a promising strategy for broad-spectrum antivirals, rescue-of-secretion therapy in rare disease caused by responsive mutations in glycoprotein genes, and many cancers, but to date no selective UGGT inhibitors are known. The small molecule 5-[(morpholin-4-yl)methyl]quinolin-8-ol (5M-8OH-Q) binds a CtUGGTGT24 “WY” conserved surface motif conserved across UGGTs but not present in other GT24 family glycosyltransferases. 5M-8OH-Q has a 47 μM binding affinity for CtUGGTGT24 in vitro as measured by ligand-enhanced fluorescence. In cellula, 5M-8OH-Q inhibits both human UGGT isoforms at concentrations higher than 750 μM. 5M-8OH-Q binding to CtUGGTGT24 appears to be mutually exclusive to M5-9 glycan binding in an in vitro competition experiment. A medicinal program based on 5M-8OH-Q will yield the next generation of UGGT inhibitors